CN106536509B - 作为组蛋白甲基转移酶和dna甲基转移酶的双重抑制剂的新型化合物 - Google Patents

作为组蛋白甲基转移酶和dna甲基转移酶的双重抑制剂的新型化合物 Download PDF

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CN106536509B
CN106536509B CN201580034131.4A CN201580034131A CN106536509B CN 106536509 B CN106536509 B CN 106536509B CN 201580034131 A CN201580034131 A CN 201580034131A CN 106536509 B CN106536509 B CN 106536509B
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compound
formula
cancer
pharmaceutically
methoxy
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CN106536509A (zh
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X·阿吉雷·埃娜
J·奥亚扎巴尔·圣玛丽娜
F·普罗斯佩尔·卡多索
M·O·拉巴尔·格雷西亚
J·R·罗德里格斯·马多
E·圣·乔斯·埃内里斯
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Fundacion para la Investigacion Medica Aplicada
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
CN201580034131.4A 2014-06-16 2015-03-30 作为组蛋白甲基转移酶和dna甲基转移酶的双重抑制剂的新型化合物 Active CN106536509B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP14382230 2014-06-16
EP14382230.2 2014-06-16
PCT/EP2015/056860 WO2015192981A1 (en) 2014-06-16 2015-03-30 Novel compounds as dual inhibitors of histone methyltransferases and dna methyltransferases

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CN106536509A CN106536509A (zh) 2017-03-22
CN106536509B true CN106536509B (zh) 2020-06-09

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US (1) US9840500B2 (es)
EP (1) EP3154957B1 (es)
JP (1) JP6527534B2 (es)
CN (1) CN106536509B (es)
AU (1) AU2015276537B2 (es)
CA (1) CA2987978C (es)
DK (1) DK3154957T3 (es)
ES (1) ES2769648T3 (es)
WO (1) WO2015192981A1 (es)

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WO2017102677A1 (en) * 2015-12-14 2017-06-22 Fundación Para La Investigación Médica Aplicada 2,4,6,7-tetrasubstituted quinoline compounds as inhibitors of dna methyltransferases
PL3442947T3 (pl) * 2016-04-15 2023-10-02 Epizyme, Inc. Związki arylowe lub heteroarylowe podstawione aminą jako inhibitory ehmt1 i ehmt2
TWI794171B (zh) 2016-05-11 2023-03-01 美商滬亞生物國際有限公司 Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療
TWI808055B (zh) 2016-05-11 2023-07-11 美商滬亞生物國際有限公司 Hdac 抑制劑與 pd-1 抑制劑之組合治療
WO2017201199A1 (en) * 2016-05-17 2017-11-23 Duke University Compositions and methods for the treatment of prader-willi syndrome
US11433068B2 (en) * 2016-09-08 2022-09-06 The General Hospital Corporation Treatment of cancers having alterations within the SWI/SNF chromatin remodeling complex
ES2910108T3 (es) * 2016-12-22 2022-05-11 Global Blood Therapeutics Inc Inhibidores de la histona metiltransferasa
WO2018119065A1 (en) 2016-12-22 2018-06-28 Asddr, Llc Use of histone methyltransferase inhibitors and histone deacetylase inhibitors for therapy of phelan-mcdermid syndrome
US20200113901A1 (en) * 2017-03-31 2020-04-16 Epizyme, Inc. Methods of using ehmt2 inhibitors
EP3612181A4 (en) 2017-04-21 2021-01-06 Epizyme, Inc. COMBINATION THERAPIES WITH EHMT2 INHIBITORS
EP3634962B1 (en) 2017-06-09 2023-05-24 Global Blood Therapeutics, Inc. Azaindole compounds as histone methyltransferase inhibitors
WO2018229139A1 (en) 2017-06-14 2018-12-20 Fundación Para La Investigación Médica Aplicada Novel compounds for use in cancer
US11661410B2 (en) 2017-08-15 2023-05-30 Global Blood Therapeutics, Inc. Tricyclic compounds as histone methyltransferase inhibitors
WO2019036384A1 (en) 2017-08-15 2019-02-21 Global Blood Therapeutics, Inc. TRICYCLIC COMPOUNDS AS HISTONE INHIBITORS METHYLTRANSFERASES
EP3697762A4 (en) * 2017-10-18 2021-04-07 Epizyme, Inc. AMINE SUBSTITUTED HETEROCYCLIC COMPOUNDS, USED AS EHMT2 INHIBITORS, SALTS THEREOF, AND THEIR METHODS OF SYNTHESIS
SG11202003162RA (en) * 2017-10-18 2020-05-28 Epizyme Inc Methods of using ehmt2 inhibitors in treating or preventing blood disorders
EP3807248A4 (en) * 2018-05-29 2021-10-27 Council of Scientific and Industrial Research BICYCLIC TOPOISOMERASE I INHIBITOR COMPOUNDS, THEIR PREPARATION AND USE
WO2019243236A1 (en) 2018-06-18 2019-12-26 Fundación Para La Investigación Médica Aplicada New anticancer drug combinations
CN112390791B (zh) * 2019-08-14 2023-08-01 复旦大学 一类dna甲基转移酶1荧光探针及其用途
US11351149B2 (en) 2020-09-03 2022-06-07 Pfizer Inc. Nitrile-containing antiviral compounds
CN115160294B (zh) * 2022-06-27 2023-09-29 中山大学 一种G9a/GLP共价抑制剂及其制备方法及应用

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WO1999001154A1 (en) * 1997-07-03 1999-01-14 University Of Iowa Research Foundation Method for inhibiting immunostimulatory dna associated responses
WO2000076982A1 (en) * 1999-06-16 2000-12-21 University Of Iowa Research Foundation Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases
CN1290698A (zh) * 1999-10-01 2001-04-11 弗·哈夫曼-拉罗切有限公司 喹啉－4－基衍生物i
WO2003055866A1 (en) * 2001-12-21 2003-07-10 Bayer Pharmaceuticals Corporation Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents
WO2004056352A1 (en) * 2002-12-19 2004-07-08 Scios, Inc. TREATMENT OF OBESITY AND ASSOCIATED CONDITIONS WITH TGF-β INHIBITORS
CN101535295A (zh) * 2006-10-12 2009-09-16 休普基因公司 用于调节dna甲基化的喹啉衍生物
CN101889008A (zh) * 2007-10-12 2010-11-17 休普基因公司 用于调节dna甲基化的喹啉衍生物
CN102596200A (zh) * 2009-11-07 2012-07-18 默克专利有限公司 作为TGF-β受体激酶抑制剂的杂芳基氨基喹啉类
CN102597218A (zh) * 2009-08-12 2012-07-18 国立大学法人京都大学 用于诱导多能干细胞分化成神经前体细胞的方法
WO2013062943A1 (en) * 2011-10-24 2013-05-02 Glaxosmithkline Intellectual Property Development Limited New compounds
WO2013140148A1 (en) * 2012-03-19 2013-09-26 Imperial Innovations Limited Quinazoline compounds and their use in therapy
WO2014072391A1 (en) * 2012-11-09 2014-05-15 St-Ericsson Sa Analog to digital conversion method with offset tracking and correction and analog to digital converter implementing the same

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DK1088818T3 (da) * 1999-10-01 2005-03-14 Hoffmann La Roche Quinolin-4-yl-derivater
EP1633718B1 (en) * 2003-06-17 2012-06-06 Millennium Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR INHIBITING TGF-s
US20080175814A1 (en) 2006-10-12 2008-07-24 Supergen, Inc. Quinoline derivatives for modulating dna methylation
TW201111376A (en) * 2009-06-25 2011-04-01 Amgen Inc Heterocyclic compounds and their uses
EP2730558A1 (en) * 2012-11-08 2014-05-14 Ikerchem, S.L. Indole derivatives, pharmaceutical compositions containing such indoles and their use as DNA methylation modulators
JP6338601B2 (ja) * 2013-03-01 2018-06-06 フンダシオン パラ ラ インベスティガシオン メディカ アプリカダ ホスホジエステラーゼとヒストンデアセチラーゼの二重阻害剤としての新規な化合物

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WO1999001154A1 (en) * 1997-07-03 1999-01-14 University Of Iowa Research Foundation Method for inhibiting immunostimulatory dna associated responses
WO2000076982A1 (en) * 1999-06-16 2000-12-21 University Of Iowa Research Foundation Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases
CN1290698A (zh) * 1999-10-01 2001-04-11 弗·哈夫曼-拉罗切有限公司 喹啉－4－基衍生物i
WO2003055866A1 (en) * 2001-12-21 2003-07-10 Bayer Pharmaceuticals Corporation Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents
WO2004056352A1 (en) * 2002-12-19 2004-07-08 Scios, Inc. TREATMENT OF OBESITY AND ASSOCIATED CONDITIONS WITH TGF-β INHIBITORS
CN101535295A (zh) * 2006-10-12 2009-09-16 休普基因公司 用于调节dna甲基化的喹啉衍生物
CN101889008A (zh) * 2007-10-12 2010-11-17 休普基因公司 用于调节dna甲基化的喹啉衍生物
CN102597218A (zh) * 2009-08-12 2012-07-18 国立大学法人京都大学 用于诱导多能干细胞分化成神经前体细胞的方法
CN102596200A (zh) * 2009-11-07 2012-07-18 默克专利有限公司 作为TGF-β受体激酶抑制剂的杂芳基氨基喹啉类
WO2013062943A1 (en) * 2011-10-24 2013-05-02 Glaxosmithkline Intellectual Property Development Limited New compounds
WO2013140148A1 (en) * 2012-03-19 2013-09-26 Imperial Innovations Limited Quinazoline compounds and their use in therapy
WO2014072391A1 (en) * 2012-11-09 2014-05-15 St-Ericsson Sa Analog to digital conversion method with offset tracking and correction and analog to digital converter implementing the same

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Antagonism of Immunostimulatory CpG-Oligodeoxynucleotides by Quinacrine, Chloroquine, and Structurally Related Compounds;Donald E. Macfarlane;《The Journal of Immunology》;19981231;第160卷;全文 *
Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human;Giuseppe A. M. Giardina;《J. Med. Chem.》;19971231;第40卷(第12期);全文 *
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Also Published As

Publication number Publication date
US9840500B2 (en) 2017-12-12
EP3154957A1 (en) 2017-04-19
CA2987978C (en) 2022-08-16
AU2015276537B2 (en) 2019-03-14
JP2017524668A (ja) 2017-08-31
AU2015276537A1 (en) 2017-01-05
DK3154957T3 (da) 2020-02-17
CN106536509A (zh) 2017-03-22
ES2769648T3 (es) 2020-06-26
CA2987978A1 (en) 2015-12-23
US20170121316A1 (en) 2017-05-04
JP6527534B2 (ja) 2019-06-05
EP3154957B1 (en) 2019-11-20
WO2015192981A1 (en) 2015-12-23

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